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CENTER VALLEY, Pa., March 19, 2024 /PRNewswire/ -- Olympus, a leading global medtech company providing innovative solutions for medical and surgical procedures, announced today it applauds the new Obesity Bill of Rights . Continue Reading Olympus applauds the newly launched Obesity Bill of Rights and will support the initiative by working to build awareness and talking to its healthcare customers about this important campaign to counter bias and ageism in obesity care. Olympus will support the initiative by working to build awareness and talking to its healthcare customers about this important campaign to counter bias and ageism in obesity care. The program, spearheaded in January 2024 in the U.S. by the National Consumers League (NCL), a nonprofit consumer advocacy group, in conjunction with the National Council on Aging (NCOA), establishes a set of rights to "assure screening, diagnosis, counseling and effective treatment based on medical treatment guidelines." This ongoing effort to gather support is expected to culminate in a fully implemented Bill of Rights by Dec. 31, 2029. The NCL and NCOA are working at the grassroots, employer, state and federal levels on this effort to ensure equal access to care for all obesity patients. NCL and NCOA worked with health leaders and obesity specialists to draft these Bill of Rights tenets that are intended to change the narrative, such that the healthcare industry more effectively sees obesity as a treatable chronic disease that can be treated with the same "respect, attention and medical care" as other chronic conditions. Statistics regarding obesity are staggering: 108M people in the U.S. are considered obese, only 10% of whom get help from medical professionals and only 2% of whom are treated with new medications. More than 230 conditions are worsened by obesity. Obesity is connected to $1.73 trillion in annual medical costs in the U.S. 400K premature deaths annually are linked to obesity.1 "Olympus provides equipment to the surgical community that helps in the treatment of obesity, and statistics show that not enough people have access to this type of treatment," said Paul Skodny, Executive Director for Health Economics and Market Access at Olympus Corporation. "It is our hope that awareness of treatment options and equitable access and insurance coverage will help address the detrimental health impacts of obesity." Bariatric Surgery as a Solution for Weight Loss Because of recent pharmaceuticals' entry into the market, such as semaglutide-based medications, obesity treatment has been receiving more attention. Surgical treatment which can complement medical management, has a lengthy track record, having been available to patients for decades with favorable long-term outcomes.2 Studies show patients typically lose the most weight one to two years after bariatric surgery and see substantial improvements in obesity-related conditions. Despite the growing number of obesity-related health problems, fewer than 2% of those eligible for bariatric surgery elect to have it.3 Given these statistics, Olympus, maker of technologies for performing minimally invasive bariatric procedures, sought to understand the awareness level and concerns of eligible patients in a survey conducted in 20194: Marginal Awareness around Benefits: A little more than 50% of respondents demonstrated only marginal awareness that bariatric surgery causes hormonal changes that improve weight loss by maintaining or enhancing energy expenditure.5 Worry about Gaining Weight Back: 20% of respondents were avoiding bariatric surgery because of concerns about surgery complications and gaining the weight back. Awareness around Insurance Opportunities: 56% of respondents were aware that insurance covers bariatric surgery in most qualified cases.6 Surgical benefits are real and should be known to more patients. Studies show that: Patients may lose as much as 60% of excess weight six months after surgery, and 77% of excess weight as early as 12 months after surgery. On average, five years after surgery, patients maintain 50% of their excess weight loss.1 The majority of bariatric surgery patients with diabetes, dyslipidemia, hypertension, and obstructive sleep apnea experience remission of these obesity-related diseases.1 Statistically, the risk of death during weight-loss surgery procedures is less than 1 percent. All abdominal operations carry the risks of bleeding, infection in the incision, thrombophlebitis of legs (blood clots), lung problems (pneumonia, pulmonary embolisms), strokes or heart attacks, anesthetic complications and blockage or obstruction of the intestine. These risks are greater in patients with severe obesity.7 To learn more about Olympus' state-of-the-art technologies for performing minimally invasive bariatric surgeries, visit the Bariatrics product page. About Olympus At Olympus, we are committed to our purpose of making people's lives healthier, safer and more fulfilling. As a global medical technology company, we partner with healthcare professionals striving to provide best-in-class solutions and services for early detection, diagnosis and minimally invasive treatment, aiming to improve patient outcomes by elevating the standard of care in targeted disease states. For more than 100 years, Olympus has pursued a goal of contributing to society by producing products designed with the purpose of delivering optimal outcomes for its customers around the world. For more information, visit medical.olympusamerica.com. _______________________________ 1 Americans now have an Obesity Bill of Rights. NCLnet.org. . Published January 31, 2024. Accessed February 29, 2024. 2 Story of Obesity Surgery. asmbs.org. . Published 2023. Accessed February 29, 2024. 3 . February 27, 2020. Accessed February 29, 2024. 4 The Olympus-commissioned online survey was conducted mid-December 2019. 5 Public Education Committee. Benefits of Bariatric Surgery: ASMBS. American Society for Metabolic and Bariatric Surgery. . Accessed February 29, 2024. 6 Manning S. How to get your health insurer to pay for your weight-loss surgery. Insure.com. . Published September 24, 2020. Accessed February 29, 2024. 7 Available Procedures. Yale New Haven Health. . Accessed March 15, 2024. SOURCE Olympus Corporation of the Americas

Featured data include new results from the Phase 3 MARIPOSA study, which has received U.S. FDA Priority Review, and the Phase 1b PALOMA study of subcutaneous amivantamab PRAGUE, March 18, 2024 /PRNewswire/ -- Johnson & Johnson announced today that new data will be featured at this year's European Lung Cancer Congress (ELCC) taking place from March 20 to 23 in Prague, Czech Republic, highlighting the Company's commitment to transform the treatment of lung cancer through the ongoing study of RYBREVANT® (amivantamab)-based regimens in the treatment of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Key data to be featured in four mini-oral presentations include results from an exploratory analysis from the Phase 3 MARIPOSA study evaluating the effect of RYBREVANT® dose interruptions on clinical outcomes, new results confirming the recommended dose for monthly subcutaneous administration of amivantamab from the Phase 1b PALOMA study, and post-progression analyses from the pivotal PAPILLON and MARIPOSA-2 studies, which aim to support the differentiated clinical profile of RYBREVANT® in the treatment of patients with EGFR-mutated NSCLC.1,2,3,4 "The breadth of data being presented at ELCC underscore our commitment to redefine treatment outcomes for patients living with EGFR-mutated NSCLC," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. "Following recent regulatory submissions in the U.S. and Europe, we look forward to advancing our transformative portfolio and bringing novel targeted treatment regimens to patients around the world." "The results presented at ELCC reinforce the role RYBREVANT-based treatment regimens may play in improving the standard of care in EGFR-mutated NSCLC," said Henar Hevia, EMEA Therapeutic Area Lead, Oncology, Solid Tumors, Johnson & Johnson Innovative Medicine. "We have made remarkable progress in advancing the science of NSCLC and will continue to evaluate the full potential of RYBREVANT as a treatment for patients through our comprehensive clinical development program." Key presentations include: Insights on the effect of RYBREVANT® plus lazertinib dose interruptions on clinical outcomes from the Phase 3 MARIPOSA study in patients with previously untreated EGFR advanced NSCLC (Abstract #1001). Results from the Phase 1 PALOMA study examining the severity and incidence of infusion-related reactions with subcutaneous amivantamab administration in patients with advanced solid tumor malignancies (Abstract #839). Data from an exploratory analysis of the Phase 3 PAPILLON study evaluating the impact of treatment with RYBREVANT® plus chemotherapy on post-progression secondary endpoints including time-to-treatment discontinuation (TTD) and time to subsequent therapy (TTST) in patients with NSCLC with EGFR exon 20 insertion mutations (Abstract #844). Analysis of post-progression outcomes including TTD, TTST, and progression-free survival after first subsequent therapy (PFS2) from the Phase 3 MARIPOSA-2 study, which is investigating RYBREVANT® plus chemotherapy in patients with EGFR-mutant advanced NSCLC after progression with osimertinib treatment (Abstract #833). The complete list of Company-sponsored abstracts follows: About RYBREVANT® RYBREVANT® (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe, and in other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.5 RYBREVANT® is also approved in the U.S. in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. In October 2023, a type II extension of indication application was submitted to the European Medicines Agency (EMA) seeking approval of RYBREVANT® for this indication. In December 2023, Johnson & Johnson submitted an sBLA together with a New Drug Application (NDA) to the U.S. FDA for RYBREVANT® in combination with lazertinib for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test. This submission is based on the Phase 3 MARIPOSA study and was granted Priority Review in February 2024. A marketing authorization application (MAA) and type II extension of indication application were also submitted to the EMA seeking approval of lazertinib in combination with RYBREVANT® based on the MARIPOSA study. In November 2023, Johnson & Johnson submitted an sBLA to the U.S. FDA for RYBREVANT® in combination with chemotherapy for the treatment of patients with EGFR-mutated NSCLC who progressed on or after osimertinib based on the MARIPOSA-2 study. A type II extension of indication application was also submitted to the EMA seeking approval of RYBREVANT® for this indication. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include: Amivantamab-vmjw (RYBREVANT®) plus carboplatin and pemetrexed as a preferred (Category 1 recommendation) first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC, or as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.6 †‡ Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a preferred (Category 1 recommendation) subsequent therapy for patients with locally advanced or metastatic NCSLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.6 †‡ Amivantamab-vmjw (RYBREVANT®) as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.6 †‡ RYBREVANT® is being studied in multiple clinical trials in NSCLC, including: The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT® in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Topline data for this randomized Phase 3 study demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients receiving RYBREVANT®.7 The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT® (with or without lazertinib) and carboplatin-pemetrexed versus carboplatin-pemetrexed alone in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC after disease progression on or after osimertinib. Topline data for this randomized Phase 3 study demonstrated statistically significant and clinically meaningful improvement in PFS in these patients receiving RYBREVANT® plus chemotherapy with and without lazertinib versus chemotherapy.8 The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT® in combination with lazertinib versus osimertinib and versus lazertinib alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations. Topline data for this randomized Phase 3 study demonstrated statistically significant and clinically meaningful improvement in PFS in patients receiving RYBREVANT® plus lazertinib versus osimertinib.9 The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT® in patients with advanced NSCLC.10 The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT® in combination with lazertinib and lazertinib as a monotherapy in patients with advanced NSCLC with EGFR mutations.11 The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab subcutaneous delivery.12 The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC.13 The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared to intravenous amivantamab in patients with EGFR-mutated advanced or metastatic NSCLC.14 The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT® and capmatinib combination therapy in locally advanced or metastatic NSCLC.15 The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT® and cetrelimab combination therapy in locally advanced or metastatic NSCLC.16 The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT® in combination with lazertinib in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.17 For more information, visit: . About Non-Small Cell Lung Cancer Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.18,19 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.20 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.21 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.20,21,22,23,24,25 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.26 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent.27,28 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.29 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.30 RYBREVANT® IMPORTANT SAFETY INFORMATION 5 WARNINGS AND PRECAUTIONS The safety population of RYBREVANT® with carboplatin and pemetrexed described in Warnings and Precautions was based on 151 patients in the PAPILLON study. The safety population of RYBREVANT® as a single agent described in Warnings and Precautions was based on 129 patients in the CHRYSALIS study. Infusion-Related Reactions RYBREVANT ® can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. RYBREVANT® with Carboplatin and Pemetrexed RYBREVANT® in combination with carboplatin and pemetrexed can cause infusion-related reactions. Based on the safety population, infusion-related reactions occurred in 42% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed, including Grade 3 (1.3%) adverse reactions. The incidence of infusion modifications due to IRR was 40%, and 0.7% of patients permanently discontinued RYBREVANT®. RYBREVANT® as a Single Agent Based on the safety population, IRR occurred in 66% of patients treated with RYBREVANT®. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4%with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62%, and 1.3% of patients permanently discontinued RYBREVANT® due to IRR. Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT® as recommended. Administer RYBREVANT® via a peripheral line on Week 1 and Week 2. Monitor patients for any signs and symptoms of infusion reactions during RYBREVANT® infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT® based on severity. Interstitial Lung Disease/Pneumonitis RYBREVANT ® can cause interstitial lung disease (ILD)/pneumonitis. RYBREVANT® with Carboplatin and Pemetrexed Based on the safety population, Grade 3 ILD/pneumonitis occurred in 2.6% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed. All patients required permanent discontinuation. RYBREVANT® as a Single Agent Based on the safety population, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT ®, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) discontinued RYBREVANT ® due to ILD/pneumonitis. Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT ® in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. Dermatologic Adverse Reactions RYBREVANT ® can cause rash (including dermatitis acneiform), pruritus and dry skin. RYBREVANT® with Carboplatin and Pemetrexed RYBREVANT® in combination with carboplatin and pemetrexed can cause dermatologic adverse reactions. Based on the safety population, rash occurred in 89% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed, including Grade 3 (19%) adverse reactions. Rash leading to dose reductions occurred in 19% of patients; 2% permanently discontinued RYBREVANT®, and 1.3% discontinued pemetrexed. RYBREVANT® as a Single Agent Based on the safety population, rash occurred in 74% of patients treated with RYBREVANT ®, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT ® was permanently discontinued due to rash in 0.7% of patients. Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT ® as a single agent. Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT ®. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free emollient cream is recommended for dry skin. If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, dose reduce, or permanently discontinue RYBREVANT ® based on severity. Ocular Toxicity RYBREVANT ® can cause ocular toxicity including keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis. RYBREVANT® with Carboplatin and Pemetrexed Based on the safety population, RYBREVANT® in combination with carboplatin and pemetrexed can cause ocular toxicity including blepharitis, dry eye, conjunctival redness, blurred vision, and eye pruritus. All events were Grade 1-2. RYBREVANT® as a Single Agent Based on the safety population, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT ®. All events were Grade 1-2. Promptly refer patients presenting with eye symptoms to an ophthalmologist. Withhold, dose reduce, or permanently discontinue RYBREVANT ® based on severity. Embryo-Fetal Toxicity Based on its mechanism of action and findings from animal models, RYBREVANT® can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT®. Adverse Reactions RYBREVANT® with Carboplatin and Pemetrexed For the 151 patients in the PAPILLON clinical trial who received RYBREVANT® in combination with carboplatin and pemetrexed, the most common adverse reactions (≥20%) were rash (90%), nail toxicity (62%), stomatitis (43%), infusion-related reaction (42%), fatigue (42%), edema (40%), constipation (40%), decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased albumin (7%), increased alanine aminotransferase (4%), increased gamma-glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and decreases in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%). Serious adverse reactions occurred in 37% of patients who received RYBREVANT® in combination with carboplatin and pemetrexed. Serious adverse reactions in ≥2% of patients included rash, pneumonia, ILD, pulmonary embolism, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified. RYBREVANT® as a Single Agent For the 129 patients in the CHRYSALIS clinical trial who received RYBREVANT® as a single agent, the most common adverse reactions (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%). Serious adverse reactions occurred in 30% of patients who received RYBREVANT®. Serious adverse reactions in ≥2% of patients included pulmonary embolism, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death. Please read the full Prescribing Information for RYBREVANT®. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc. are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of RYBREVANT® (amivantamab-vmjw) and lazertinib. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc. and Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments. †See the NCCN Guidelines for detailed recommendations, including other treatment options. ‡The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories. §The NCCN Content does not constitute medical advice and should not be used in place of seeking professional medical advice, diagnosis or treatment by licensed practitioners. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 1 Campelo et al. Effect of Amivantamab Dose Interruptions on Efficacy and Safety of First-line Amivantamab Plus Lazertinib in EGFR-mutant Advanced NSCLC: Exploratory Analyses from the MARIPOSA study, a Randomized Phase 3 Global Study. European Lung Cancer Congress 2024. March 2024. 2 Leighl et al. Subcutaneous amivantamab administered every 4 weeks (Q4W) in patients with advanced solid malignancies: The phase 1b PALOMA study, a Randomized Phase 1 Global Study. European Lung Cancer Congress 2024. March 2024. 3 Felip et al. Amivantamab Plus Chemotherapy vs Chemotherapy as First-Line Treatment in EGFR Exon 20 Insertion-mutated Advanced NSCLC: Analysis of Post-Progression Endpoints From PAPILLON, a Randomized Phase 3 Global Study. European Lung Cancer Congress 2024. March 2024. 4 Gentzler et al. Amivantamab Plus Chemotherapy vs Chemotherapy in EGFR-mutant Advanced NSCLC After Progression on Osimertinib: A Post-progression Analysis of MARIPOSA-2, a Randomized Phase 3 Global Study. European Lung Cancer Congress 2024. March 21, 2024. 5 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 6 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.1.2024© National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed March 2024. 7 ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions (PAPILLON). Available at: . Accessed March 2024. 8 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2). Available at: . Accessed March 2024. 9 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). Available at: . Accessed March 2024. 10 ClinicalTrials.gov. A Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS). . Accessed March 2024. 11 ClinicalTrials.gov. A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). . Accessed March 2024. 12 ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). Available at: . Accessed March 2024. 13 ClinicalTrials.gov. A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (PALOMA-2). . Accessed March 2024. 14 ClinicalTrials.gov. A Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3). . Accessed March 2024. 15 ClinicalTrials.gov. A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark). . Accessed March 2024. 16 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer (PolyDamas). . Accessed March 2024. 17 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). . Accessed March 2024. 18 The World Health Organization. Cancer. . Accessed March 2024. 19 American Cancer Society. What is Lung Cancer? . Accessed March 2024. 20 Oxnard JR, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013 Feb;8(2):179-84. doi: 10.1097/JTO.0b013e3182779d18. 21 Bauml JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 22 Pennell NA, et al. A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol. 37:97-104. 23 Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 24 Zhang YL, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993. 25 Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res. 2015;5(9):2892-2911. 26 American Lung Association. EGFR and Lung Cancer. . Accessed March 2024. 27 Howlader N, et al. SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD, , based on November 2018 SEER data submission, posted to the SEER web site. 28 Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol. 2016 Apr;11(4):556-65. 29 Arcila, M. et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013 Feb; 12(2):220-9. 30 Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. SOURCE Johnson & Johnson

An engineer experienced with radiofrequency (RF) ablation systems might wonder what all the fuss is about when looking at the design of a pulsed field ablation (PFA) system. Compared to an RF ablation generator, a PFA generator is going to look much less complicated, perhaps with only a tenth as many parts. But the seemingly simpler schematics can be deceiving. “The difference is that in a PFA power supply, the way that those components are being used is just so different, and they’re being stressed to the limits of what their ratings are in a way that just isn’t obvious to most engineers,” said Dan Friedrichs, an engineer at Minnetronix Medical. “… There’s more complexity than meets the eye.” Friedrichs leads development engineering efforts at Minnetronix Medical for the commercialization of surgical energy devices. He’s also shared his expertise with Medical Design & Outsourcing readers through several contributions on the topic. As the first PFA systems win FDA approval for treating atrial fibrillation (AFib), we asked Friedrichs and his colleague, Aaron McCabe (who, as Minnetronix’s technology segment director, focuses on surgical energy applications), to explain some of the design considerations for PFA generators. These generators send energy pulses through catheters inside the heart to disrupt erratic cardiac cells. “Some of the specs for these PFA systems require that you pick just these enormous transistors, even though the transistors aren’t processing a lot of power — they don’t actually get hot,” Friedrichs said. “… You open the lid of one of these power supplies and see these giant transistors, but they aren’t mounted to heat sinks. They aren’t processing any large amount of power, but those are the types of parts that you have to select to meet what turns out to be very esoteric requirements around delivering the types of pulses that are necessary in PFA.” “And that extends basically to all the components. Something like a capacitor inside a PFA generator that has these really strong pulsed currents that are uncommon in most other power supplies, you have to select just the right type of capacitor for it,” Friedrichs continued. “Every electronic component that goes into the power supply superficially looks very easy, but to actually get it to work, there’s all sorts of tricks that are not obvious.” PFA generators and catheters create energy fields that can open temporary or permanent holes in the walls of targeted heart cells through a process called electroporation without heat or damage to nearby nerves. A PFA procedure for AFib can be completed hours faster than the same procedure with RF, while it has less risk of damaging surrounding tissue because it’s nonthermal. “If you were to look at the outputs of these PFA systems, a typical specification could be 2,000 volts and 100 or 200 amps,” Friedrichs said. “You’d say, ‘Oh my gosh, that’s 200 kilowatts of power. Are we going to vaporize the patient when we connect this to them?’ But it turns out that the duty cycle is very short, like 1% or 2% on time, so the average power delivered to the patient is a watt or two at most. It’s not a thermal effect. But to design a power supply that’s capable of supporting those instantaneous high voltages and those instantaneous high currents. That’s actually a technical challenge.” “Because of those really high instantaneous voltages and currents, there is consideration for how do you, for example, route cables within a box, because high currents flowing through cables create magnetic fields, they interact with other components,” Friedrichs continued. “So the tolerances and the design controls that you need to go through to ensure that you get a consistent repeatable result are significant and probably not obvious.” The right recipe for PFA With RF ablation, there’s generally only one variable to control when a thermal catheter is in the heart: time. “We don’t want to create steam in the heart, so we set the temperature just below 100°C, just below boiling. Then it’s just a matter of time, because time and temperature together is what damages tissue. But that’s also the reason why these are long procedures,” Friedrichs said. Time is just one variable with PFA, and the pulses are generally measured in microseconds or milliseconds. “With PFA we have literally an infinite number of permutations of the variables,” Friedrichs said. “We have the pulse amplitude, we have the pulse width, we have the spacing between the pulses, we have the number of pulses, we have the polarity of the pulses, often there will just be arbitrary delays between different pulses, there’s recipes that have different amplitudes of pulses. Those are the parameters that vary — and that’s just on the generator, and then we connect it to a catheter and the catheter’s geometry can vary as well. We have not only an infinite space of variables that can be tuned to this, but then it’s also really hard to measure which of those given recipes is effective.” While the voltage is generally thousands of volts, the more important measure is volts per centimeter: field strength, which can be modified by changing the spacing between electrodes on the catheter. The amplitude of the pulses is “probably the strongest lever in getting the tissue selectivity that we want,” Friedrichs said, referring to PFA’s ability to ablate only heart muscle cells while sparing nearby nerves in the esophagus. “But then also it’s the width of the pulse,” he continued. “We’re applying a pulse that has an amplitude and a duration. We have a delay time before we deliver the next pulse in the sequence, and that can be different than the pulse width. Then there’s the number of pulses we apply. The pulses don’t all have to be the same polarity — for instance, we can have positive pulses, then we can have a negative pulse, or we could have two positive pulses and then a lower amplitude but longer negative pulse. And so all those combinations become an infinite number of permutations.” The timing of pulses can help counteract muscle stimulation, one of PFA’s potential side effects. That could trigger a heart contraction (or systole) or cause a patient to cough, which in turn could cause trauma if they’re on a ventilator. “The difference is between a heart defibrillator and one of these systems [is] timing,” Friedrichs said. “Can we rely on software to get the timing correct 100% of the time, or do we think that there’s a one in a million chance that the software might crash while we’re delivering the therapy to this patient?” To avoid that risk of a crash, a device developer might instead write code on a field programmable gate array (FPGA) or implement the control in purely discrete analog circuitry. “Good partitions between software and hardware enable confidence and safety,” McCabe said. And while PFA catheters are usually larger than RF ablation catheters — meaning more risk for accidental mechanical damage within the heart — PFA’s nonthermal and tissue-selective therapy is a big step forward in safety. “Even if the only thing that PFA gives us is safety against accidentally burning the esophagus — which is, to begin with a rare situation, maybe a one-in-1000 type of situation — even that is valuable enough to make this wholesale change in this multi-billion-dollar market,” Friedrichs said. Designing PFA systems for flexibility “We have so many variables, and we don’t have a good understanding of which variables are important,” Friedrichs said. “… When you compare it to legacy technologies like RF ablation, RF ablation has a lot less concern about process control in production of equipment, because we can actually measure what’s happening in the tissue. We literally have a temperature sensor in the tissue and we can measure that it’s being effective, and the variation back in the generator, it almost doesn’t matter. But with PFA, we don’t have the ability to detect that in the tissue. And then we also don’t have the ability to assess efficacy in real-time. So we’re really relying entirely on the recipe of how the pulse generator was built to be consistent and to give the same thing for every patient.” In the design phase, that requires flexibility to dial in the appropriate dose titration for effective therapy, said McCabe. “Unless you’re fortunate enough to work at one of the places that has already cracked it and have their own proprietary methods for treating, more than likely you’re at the beginning of that journey and you want to be able to dial in and alter the different parameters of your pulse,” McCabe said. “You’ve got kind of two sides of the same coin here: you need a lot of flexibility, and then you need to transition to be able to also lock down consistently and repeatedly once you’ve nailed it.” Because there aren’t a lot of electronics operating with similar parameters as PFA generators, device designers may need to consider customized components. “One of the challenges we face on all surgical energy systems is that we have to electrically isolate the patient from mains power for safety,” Friedrichs said. “Components like transformers, digital isolators and isolated power supplies don’t exist specifically for this type of system. That requires us to be very creative and either design our own or adapt something on the market to fit these unique requirements.” The future of PFA While PFA in its current form is generating excitement for its speed and safety, one issue on safety regulators’ radar is bubble formation inside the heart during treatment. Bubbles — like those created by boiling blood above 100°C with thermal ablation — create a risk of embolism, and PFA system developers such as Abbott have discussed the risks with the FDA. “There’s other mechanisms by which you could have bubbles,” Friedrichs said. “You’ve got voltage in a ionic solution — you can create electrolysis, separating ions and create chemical reaction products that way. It’s also possible to have very, very localized heating because these electrodes may have sharp edges, and so you could have hotspots there. I think the science is unsettled as to how significant of an issue this could be. But it’s unavoidable.” Friedrichs said he’s interested to see how PFA will develop in the years ahead. While thermal fields are very difficult to model computationally, the equations for electric fields are simple. “You can imagine a future where we are able to analytically plan out what kind of energy dosage we want to give a patient because right now, it’s more or less, ‘You have this disease, you are getting this dose.’ It’s not patient specific, it’s not titrated to the extent of their disease,” Friedrichs said. “But in the future, you can imagine that we would be able to actually come up with a patient-specific energy prescription and deliver it just for that patient’s disease. And that’s unique to electric fields.”